Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000464366 | SCV000547756 | pathogenic | Fanconi anemia | 2024-01-22 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 435 of the FANCA protein (p.Arg435His). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Fanconi anemia (PMID: 19367192; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 408183). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt FANCA protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects FANCA function (PMID: 29098742). This variant disrupts the p.Arg435 amino acid residue in FANCA. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10090479, 11739169, 12444097, 15523645). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
Sema4, |
RCV000464366 | SCV002534910 | likely pathogenic | Fanconi anemia | 2021-11-06 | criteria provided, single submitter | curation | |
Baylor Genetics | RCV001256354 | SCV003836279 | pathogenic | Fanconi anemia complementation group A | 2022-02-19 | criteria provided, single submitter | clinical testing | |
Leiden Open Variation Database | RCV001256354 | SCV001425785 | pathogenic | Fanconi anemia complementation group A | 2020-02-28 | no assertion criteria provided | curation | Curator: Arleen D. Auerbach. Submitter to LOVD: Sue Richards. |